Nightly application of testosterone transdermal (TTD) system to nonscrotal sites in men with hypogonadism results in a 24-hour serum testosterone concentration profile which mimics the circadian pattern observed in healthy young men. The system also normalises dihydrotestosterone/testosterone and estradiol/testosterone ratios and reduces luteinising hormone levels towards the normal range. A multicentre, open-label study demonstrated that nocturnal erectile response and overall sexual function improved during 12 months' treatment with the TTD system (5 mg/day) in men with hypogonadism. Individual variables of sexual desire, arousal, frequency of sexual activity, orgasm and satisfaction also improved. The TTD system is well tolerated, with application site reactions such as pruritus, burn-like blisters and erythema being the most commonly reported events. Prostate-specific antigen levels and prostate volume remain in the normal range during long term treatment.